Current strategies for articular cartilage repair involving ex vivo cell culture have proven complex and expensive. Recently, the sponsor laboratory has proposed an in situ approach utilizing coagulated, autologous bone marrow to fill cartilage defects and provide a biocompatible scaffold for endogenous repair. The overall goal of this research is to systematically develop and characterize an in vivo protocol involving transient delivery of chondrogenic and extracellular matrix (ECM)-stimulating factors for effective repair using bone marrow plugs. The following specific aims will be addressed: 1) Using rabbit chondroprogenitor cells within aggregate culture, to identify an optimal protocol for cartilaginous tissue formation via transient co- administration of chondrogenic and ECM-stimulating factors. 2) Based on aim 1 results, to determine transgene expression and cartilaginous tissue formation following viral delivery of chondrogenic and ECM- stimulating factor cDNAs to chondroprogenitors. 3) To characterize transgene expression and cartilaginous tissue formation following viral delivery to rabbit marrow plugs cultured in vitro. 4) Using a rabbit model, to evaluate repair of chondral and osteochondral cartilage defects in vivo by gene-activated marrow clots. [unreadable] [unreadable] [unreadable]